Modified polynucleotides

A composition comprising:

• a plurality of lipid nanoparticles comprising a cationic lipid, a PEGylated lipid, cholesterol, and a phospholipid, wherein the mean particle size of the plurality of lipid nanoparticles is 80 nm to 160 nm and the lipid nanoparticles encapsulate a polynucleotide,
• wherein the polynucleotide comprises;
• (a) a first region of linked nucleosides, said first region encoding factor IX, wherein said first region of linked nucleosides consists of nucleotides selected from 1-methyl-pseudouridine, cytidine, adenosine, and guanosine;
• (b) a first flanking region located at the 5′-terminus of said first region comprising;
• (i) a 5′-untranslated region (5′-UTR);
• and
• (ii) 5′ terminal cap;
• (c) a second flanking region located at the 3′-terminus of said first region comprising;
• (i′) a 3′-untranslated region (3′-UTR);
• and
• (ii′) a 3′-tailing sequence of linked nucleosides.